title: Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT.
abstract: There is conflicting evidence on the predictive role of KRAS status when cetuximab is added to oxaliplatin-based regimens. This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients enrolled in TEGAFOX-E (cetuximab, oxaliplatin and oral uracil/ftorafur--UFT) phase II study. Twenty-eight patients were enrolled and all were evaluable for safety and activity. Twenty-three specimens were analysed for KRAS, BRAF, NRAS, PI3KCA and TP53 mutational status by means of polymerase chain reaction and correlated with objective response, progression-free survival and overall survival. An evident increase of response rate was noted in KRAS/NRAS wild-type cases (70 versus 33%, P = 0.198). KRAS/NRAS wild-type status showed an independent association with a longer progression-free survival (44 versus 9 weeks, P = 0.009). Considering the combined assessment of BRAF, KRAS/NRAS and TP53, a trend towards an increase of response rate was noted in patients without mutations (83 versus 33%, P = 0.063). Moreover, patients with all wild-type genes had significantly longer progression-free survival than patients with any mutation (48 versus 10 weeks, P = 0.007). As a single biomarker, only KRAS/NRAS proteins maintained an independent value for outcome prediction. Patients with KRAS/NRAS, BRAF and TP53 wild-type tumours could derive the maximal benefits from treatment with cetuximab, oxaliplatin and UFT.
authors.affiliation: Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133, Milan, Italy, maria.dibartolomeo@istitutotumori.mi.it.
authors.forename: M
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: F
authors.initials: F
authors.lastname: Pietrantonio
authors.forename: F
authors.initials: F
authors.lastname: Perrone
authors.forename: K F
authors.initials: KF
authors.lastname: Dotti
authors.forename: A
authors.initials: A
authors.lastname: Lampis
authors.forename: C
authors.initials: C
authors.lastname: Bertan
authors.forename: E
authors.initials: E
authors.lastname: Beretta
authors.forename: L
authors.initials: L
authors.lastname: Rimassa
authors.forename: C
authors.initials: C
authors.lastname: Carbone
authors.forename: P
authors.initials: P
authors.lastname: Biondani
authors.forename: R
authors.initials: R
authors.lastname: Passalacqua
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.forename: E
authors.initials: E
authors.lastname: Bajetta
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D005641:Tegafur / Q000008:administration & dosage; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014498:Uracil / Q000008:administration & dosage; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009944:Organoplatinum Compounds; C503859:PI3KCA protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D005641:Tegafur; D014498:Uracil; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab